.beta.-Lactam antibiotics are a group of antibiotics which are used for treatment of infectious diseases caused by Gram-positive, Gram-negative, aerobic, and anaerobic bacteria. .beta.-Lactam antibiotics are also used for the prevention of bacterial infection. Due to their high efficacy and safety, .beta.-lactam antibiotics have been the most frequently used antimicrobial agent in many countries for the last few decades. Typical examples of clinically used .beta.-lactam antibiotics are benzylpenicillin (penicillin G), phenoxymethylpenicillin (penicillin V), ampicillin, carbenicillin, and piperacillin, which are classified into the penicillin group; cephalothin, cephalexin, cefazolin, cephalothin, cefotaxime, ceftadizime, and ceftriaxon; which belong to the cephalosporin group; aztreonam and carmonam, which are known as monobactams; and imipenem, a member of the carbapenem class.
.beta.-Lactamases, a group of enzymes which destroy .beta.-lactam antibiotics by hydrolysing the .beta.-lactam ring and make antibiotics inactive, have been known to be produced by certain bacteria from the very early stage of the history of .beta.-lactam antibiotics as chemotherapeutic agents. After heavy usage of .beta.-lactam antibiotics, the frequency of bacterial resistance caused by .beta.-lactamase-production grew rapidly. The number of isolated members of .beta.-lactamases also expanded rapidly and its number is still continuously growing.
Substances which can inhibit .beta.-lactamases are called .beta.-lactamase inhibitors. The effectiveness of conventional .beta.-lactamase-susceptible .beta.-lactam antibiotics can be enhanced by concomitant usage of such .beta.-lactamase inhibitors. Three such inhibitors, clavulanic acid, sulbactam, and tazobactam are currently available on the market in combination with amoxycillin, ampicillin, and piperacillin, respectively (Antimicrob. Agents Chemother. 1977, 11, 852, Antimicrob. Agents Chemother. 1978, 14, 414, J. Med. Chem. 1987, 30, 1074). Although these inhibitors proved to enhance the effectiveness of conventional antibiotics against many bacteria, they failed to protect the antibiotics from one of the major classes of .beta.-lactamases, which are known as chromosomally encoded inducible cephalosporinases or class C cephalosporinases. Due to the frequent use of the newer generation of cephalosporin antibiotics in clinics, the number of incidents of bacterial resistance caused by class C cephalosporinases is increasing. Some cephalosporin derivatives which are capable of inhibiting the cephalolsporinases are reported (Antimicrob. Agents Chemother. 1982, 21, 613).